Regulation and diversity of ligands for NK receptors in immunity and autoimmune diseases

• Project/Area Number: 24590398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NARUSE Taeko 東京医科歯科大学, 難治疾患研究所, 助教 (80422476)
• Co-Investigator(Kenkyū-buntansha): KIMURA Akinori 東京医科歯科大学, 難治疾患研究所, 教授 (60161551)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: NKレセプターリガンド / ULBP / DNAメチル化 / ゲノム多様性 / 遺伝子発現 / NKレセプター / リガンド / ULBP遺伝子 / 自己免疫疾患 / 連鎖不平衡ブロック

Outline of Final Research Achievements

Natural-killer group 2 member D (NKG2D), a C-type lectin molecule, is an activating receptor. In human, UL-16 binding protein (ULBP) / retinoic acid early transcript 1 (REAT1) family are known to encode ligands for NKG2D. The human ULBP gene family is composed of six functional members, ULBP1-ULBP6. In the present study, we found that the ULBP4 expression in colon cancer cell lines were inversly correlated with methylation level of the ULBP4 gene, indicating that the difference in methylation pattern may differently contribute to the regulation of NK function. In addition, we identified polymorphisms in ULBP2 and ULBP5 genes from rhesus and crab-eating macaques. It was suggested that the Old World monkeys are good animal models for developping the immune regulation by ULBPs.

Research Products

• [Journal Article] APOBEC3H polymorphisms associated with susceptibility to HIV-1 infection and AIDS progression in Japanese. (2015)
  • Author(s): Sakurai D, Iwatani Y, Ohtani H, Naruse TK, Terunuma H, Sugiura W, Kimura A.
  • Journal Title: Immunogenetics Volume: 67 Issue: 4 Pages: 253-257
  • DOI: 10.1007/s00251-015-0829-2
  • Peer Reviewed
• [Journal Article] Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model. (2014)
  • Author(s): Nomura T, Yamamoto H, Takahashi N, Naruse TK, Kimura A, Matano T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 450 Issue: 2 Pages: 942-947
  • DOI: 10.1016/j.bbrc.2014.06.072
  • Peer Reviewed
• [Journal Article] Divergence and diversity of ULBP2 genes in rhesus and cynomolgus macaques (2014)
  • Author(s): Naruse TK, Akari H, Matano T, Kimura A.
  • Journal Title: Immunogenetics Volume: 66 Issue: 3 Pages: 161-170
  • DOI: 10.1007/s00251-014-0760-y
  • Peer Reviewed / Open Access
• [Journal Article] A DFNA5 Mutation Identified in Japanese Families with Autosomal Dominant Hereditary Hearing Loss (2014)
  • Author(s): Nishio A, Noguchi Y, Sato T, Naruse T, Kimura A, Takagi A, Kitamura K
  • Journal Title: Ann Hum Genet Volume: 78 Issue: 2 Pages: 83-91
  • DOI: 10.1111/ahg.12053
  • Peer Reviewed
• [Journal Article] Control of SIV replication by vaccine-induced Gag- and Vif-specific CD8+ T cells (2014)
  • Author(s): Nami Iwamoto, Naofumi Takahashi, Sayuri Seki, Takushi Nomura, Hiroyuki Yamamoto, Makoto Inoue, Tsugumine Shu, Taeko K. Naruse, Akinori Kimura, and Tetsuro Matano
  • Journal Title: J. Virol. Volume: 88 Issue: 1 Pages: 425-433
  • DOI: 10.1128/jvi.02634-13
  • Peer Reviewed
• [Journal Article] Limited impact of passive non-neutralizing antibody immunization in acute SIV infection on viremia control in rhesus macaques (2013)
  • Author(s): Taku Nakane, Takushi Nomura, Shoi Shi, Midori Nakamura, Taeko K. Naruse, Akinori Kimura, Tetsuro Matano, and Hiroyuki Yamamoto
  • Journal Title: PLoS ONE Volume: 8 Issue: 9 Pages: e73453-e73453
  • DOI: 10.1371/journal.pone.0073453
  • Peer Reviewed
• [Journal Article] Two Susceptibility Loci to Takayasu Arteritis Reveal a Synergistic Role of the IL12B and HLA-B Regions in a Japanese Population (2013)
  • Author(s): Terao C, Yoshifuji H, Kimura A, Matsumura T, Ohmura K, Takahashi M, Shimizu M, Kawaguchi T, Chen Z, Naruse TK, Sato-Otsubo A, Ebana Y, Maejima Y, Kinoshita H, Murakami K, Kawabata D, Wada Y, Narita I,
  • Journal Title: American Journal of Human Genetics Volume: 93 Issue: 2 Pages: 289-297
  • DOI: 10.1016/j.ajhg.2013.05.024
  • Peer Reviewed
• [Journal Article] Diversity of MHC class I genes in rhesus macaques and cynomolgus macaques (crab-eating monkeys) (2013)
  • Author(s): 成瀬妙子、木村彰方
  • Journal Title: Major Histocompatibility Complex Volume: 20 Issue: 1 Pages: 35-44
  • DOI: 10.12667/mhc.20.35
  • NAID: 130004647537
  • ISSN: 2186-9995, 2187-4239
  • Peer Reviewed
• [Journal Article] Status of TIM-1 exon 4 haplotypes and CD4+T cell counts in HIV-1 seroprevalent North Indians. (2013)
  • Author(s): Sharma G, Ohtani H, Kaur G, Naruse TK, Sharma SK, Vajpayee M, Kimura A, Mehra NK.
  • Journal Title: Hum Immunology Volume: 7 Issue: 2 Pages: 163-165
  • DOI: 10.1016/j.humimm.2012.11.013
  • Peer Reviewed
• [Journal Article] Lineage-specific evolution of T-cell immunoglobulin and mucin domain 1 gene in the primates (2012)
  • Author(s): Ohtani, H., Naruse, T.K., Iwasaki, Y., Akari, H., Ishida, T., Matano, T. and Kimura, A
  • Journal Title: Immunogenetics Volume: 64 Issue: 9 Pages: 669-678
  • DOI: 10.1007/s00251-012-0628-y
  • Peer Reviewed
• [Presentation] 抗HIV 薬投与下の治療ワクチン接種により誘導されるCD8 陽性T 細胞のSIV 複製 (2014)
  • Author(s): 中村碧、高原悠佑、松岡佐織、三浦智行、小柳義夫、成瀬妙子、木村彰方、俣野哲朗
  • Organizer: 第28回日本エイズ学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2014-12-05
• [Presentation] 霊長類におけるULBP 5/ RAET1-G遺伝子群の進化 (2014)
  • Author(s): 成瀬妙子、飯塚淳次、明里宏文、俣野哲朗、木村彰方
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: タワーホール船堀（東京都・江戸川区）
  • Year and Date: 2014-11-20
• [Presentation] 霊長類におけるULBP/RAET1遺伝子群の進化と特徴 (2014)
  • Author(s): 成瀬妙子、飯塚淳次、明里宏文、俣野哲朗、木村彰方
  • Organizer: 23回日本組織適合性学会大会
  • Place of Presentation: 長崎大学医学部キャンパス（長崎県・長崎市）
  • Year and Date: 2014-09-14
• [Presentation] 旧世界ザルULBP2/RAET1H遺伝子の種特異的多様性． (2013)
  • Author(s): 成瀬妙子、森 一泰、明里宏文、俣野哲朗、木村彰方．
  • Organizer: 第22回日本組織適合性学会
  • Place of Presentation: こらっせ福島
• [Presentation] 旧世界ザルULBP2/RAET1H遺伝子の種特異的多様性． (2013)
  • Author(s): 成瀬妙子、森 一泰、明里宏文、俣野哲朗、木村彰方．
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 江陽グランドホテル
• [Presentation] サルエイズモデルにおける抗HIV薬投与下のCTL誘導治療ワクチン接種によるSIV増殖抑制能の増強効果の解析． (2013)
  • Author(s): 中村 碧、高原悠佑、松岡佐織、三浦智行、小柳義夫、成瀬妙子、木村彰方、俣野哲朗．サ
  • Organizer: 第61回日本ウイルス学会学術集会．
  • Place of Presentation: 神戸国際会議場
• [Presentation] NFKBIL1はヒトおよびウイルス遺伝子のスプライシングを制御する. 第21回日本組織適合性学会 (2012)
  • Author(s): 安 健博、中島敏晶、柴田宏樹、成瀬妙子、有村卓朗、安波道郎、木村彰方
  • Organizer: 第21回日本組織適合性学会
  • Place of Presentation: 東京
• [Presentation] アカゲザルULBP2/RAET1H遺伝子の多様性解析 (2012)
  • Author(s): 成瀬妙子、森 一泰、明里宏文、俣野哲朗、木村彰方
  • Organizer: 第21回日本組織適合性学会
  • Place of Presentation: 東京
• [Presentation] HIV/AIDS感受性の個体差とKIR, HLA遺伝子多型 (2012)
  • Author(s): 成瀬妙子、小西真紀子、柳田梨紗、照沼 裕、 Gaurav Sharma, Gurvinder Kaur, Narinder K Mehra, 木村彰方
  • Organizer: 第21回日本組織適合性学会
  • Place of Presentation: 東京
• [Presentation] 霊長類におけるTIM1遺伝子進化とHIV/AIDS (2012)
  • Author(s): 木村彰方、大谷仁志、成瀬妙子、Gaurav Sharma, Gurvinder Kaur, Narinder K Mehra,明里宏文、石田貴文、俣野哲朗
  • Organizer: 第21回日本組織適合性学会
  • Place of Presentation: 東京
• [Presentation] HLA領域内のNFKBIL1はヒトおよびウイルス遺伝子の選択的スプライシングを制御する (2012)
  • Author(s): 安 健博、中島敏晶、柴田宏樹、成瀬妙子、有村卓朗、安波道郎、木村彰方
  • Organizer: 日本人類遺伝学会 第57回大会
  • Place of Presentation: 東京
• [Presentation] 旧世界ザルULBP2/RAET1H遺伝子の多様性解析 (2012)
  • Author(s): 成瀬妙子、森 一泰、明里宏文、俣野哲朗、木村彰方
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 東京